Since the establishment of the Cooperative Family Registry for Breast Cancer Studies (CFRBCS) in 1995, scientists at the Northern California Family Registry have contributed substantially to developing a coordinated approach among the consortium members and standardizing protocols and data collection instruments, participated in several studies and publications using the CFRBCS resource, and developed methods to estimated the number of BRCA1/2 mutation carriers in the CFRBCS families. The Northern California Family Registry made a major contribution to the data and biospecimen resources in CFRBCS, and recruited most of the minority families currently in CFRBCS. Through the population-based SEER cancer registry in the Greater San Francisco Bay area, we have identified 8,874 women and men with newly diagnosed breast cancer between 1995 and 1998. Through screening and sampling we identified 1,981 eligible probands, including all high-risk cases and a sample of sporadic cases. Of these, about 20% meet the high- risk eligibility criteria information from 1,207 probands and 1,467 first- degree relatives. Of these, 94% of probands and 75% of family members also completed the diet questionnaire. We have collected blood or mouthwash samples from 1,109 probands and 1,432 relatives, and pathology specimens from 630 probands and 42 affected relatives. The pathology review and preparation of slides for the CFRBCS archives has been completed for 450 individuals. In addition, we have recruited 147 population-based controls and have re-contacted 650 probands for our annual follow-up. We have also significantly added to the CFRBCS resource by transforming cryopreserved lymphocytes from 695 probands. The objectives of this five year grant are to: 1) Maintain the current infrastructure of the Family Registry by continued updating, of our database; adding pathology material to the repository; following all family members for vital status, recurrence of breast cancer, and new cancers; and participating in quality control and collaborative planning activities. 2) Compare all work on currently eligible families (i.e., pathology work; finish recruiting eligible minority families; finish processing blood samples for probands and population controls; complete BRCA1/2 mutation testing; and complete transformation of all lymphocytes. 3) Accrue an additional 1,060 minority and 450 Ashkenazi Jewish families, and extend recruitment for 25 families. 4) Participate in all 13 consortium research studies associated with these grants, and provide the leadership for Module 3 (BRCA1/2 in minority families) and Module 4(environmental modifiers) which are presented with our U-01. In addition, we will make major statistical contributions to Modules 8, 910, and 11; collect new data for Modules 1, 5, 6, 7, 8, 9, and 12; and conduct laboratory analyses for module 11.